Original Article

Topiramate for the Treatment of Dually Dependent on Opiates and Cocaine: A Single-center Placebo-controlled Trial


Background: Topiramate facilitates gamma aminobutyric acid (GABA) transference and an ideal candidate for reducing cocaine use in methadone patients. The present study evaluated topiramate in Dual dependence on opiate and cocaine.

Methods: This placebo-controlled study (Clinical Trial Registration Code: TCTR20170201001) conducted during the period 2013–2014, Cocaine-dependent individuals maintained on methadone (n=50) were randomized to receive topiramate or identical placebo capsules. Participants' dosage ranged between 25-300 mg/day (12 wk) in escalating doses. Methadone Doses started at 30 mg/day (median 100 mg/day; range 20 –140 mg/day). In addition, all subjects received brief behavioral compliance enhancement treatment (BBCET). The data were analyzed by Chi-square Test, generalized estimating equations (GEE) models, linear mixed effects (LME) model and Analysis of covariance (ANCOVA). Primary outcome measures included twelve weekly urine drug screens (cocaine abstinence, detection of benzoylecgonine) and treatment retention. Secondary outcome measures included correlation between cocaine craving with cocaine urine samples and Side effects of depression.

Results: Topiramate was not better than placebo in reducing cocaine use. The secondary outcome showed that Topiramate was better than placebo in reducing cocaine craving. The mean [99% confidence interval (CI)] scores of cocaine craving were 24.31 (18.61–30.01) in experimental group and 21.84 (16.86–26.81) in control group (all P > 0.01). Retention and correlation between cocaine craving and cocaine urine samples were not significantly different between the groups. Topiramate usage was not associated with increase in depression symptoms as a side effect (P>0.05).

Conclusion: The efficacy of topiramate in cocaine treatment is limited and needs the similar controlled clinical trials and can be used as a complementary intervention.


Alinejad S, Ghaemi K, Abdollahi M, Mehrpour O (2016). Nephrotoxicity of methadone: a systematic review. Springerplus, 5(1):2087.

Eizadi-Mood N, Naeini SA, Hedaiaty M et al (2016). Prevalence of pulmonary edema among the deceased cases with acute Methadone poisoning: A report from Iran. J Res Pharm Pract, 5(4):290-293.

Dobler-Mikola A, Hättenschwiler J, Meili D et al (2005). Patterns of heroin, cocaine, and alcohol abuse during long-term methadone maintenance treatment. J Subst Abuse Treat, 29(4):259-65.

Kamal F, Flavin S, Campbell F et al (2007). Factors affecting the outcome of methadone maintenance treatment in opiate dependence. Ir Med J, 100(3):393-7.

Márquez J, Campos-Sandoval JA, Peñalver A et al (2017). Glutamate and Brain Glutaminases in Drug Addiction. Neurochem Res, 42(3):846-857.

Pirnia B, Moradi AR, Pirnia K et al (2017). A Novel Therapy for cocaine dependence during abstinence: A randomized clinical trial. Electron Physician, 9(7):4862–71.

Minozzi S, Cinquini M, Amato L et al (2015). Anticonvulsants for cocaine dependence. Cochrane Database Syst Rev, (4):CD006754.

Soyka M, Mutschler J (2016). Treatment-refractory substance use disorder: Focus on alcohol, opioids, and cocaine. Prog Neuropsychopharmacol Biol Psychiatry, 70:148-61.

Kampman KM, Pettinati H, Lynch KG et al (2004). A pilot trial of topiramate for the treatment of cocaine dependence. Drug Alcohol Depend, 75(3):233-40.

Michalak A, Biała G (2016). Alcohol dependence-Neurobiology and treatment. Acta Pol Pharm, 73(1):3-12.

de Brito AM, de Almeida Pinto MG, Bronstein G et al (2017). Topiramate Combined with Cognitive Restructuring for the Treatment of Gambling Disorder: A Two-Center, Randomized, Double-Blind Clinical Trial. J Gambl Stud, 33(1):249-263.

Grilo CM, Reas DL, Mitchell JE (2016). Combining pharmacological and psychological treatments for binge eating disorder: current status, limitations, and future directions. Curr Psychiatry Rep, 18(6):55.

Kampman KM, Pettinati HM, Lynch KG et al (2013). A double-blind, placebo-controlled trial of topiramate for the treatment of comorbid cocaine and alcohol dependence. Drug Alcohol Depend, 133(1):94-9.

Johnson BA, Ait-Daoud N, Bowden CL et al (2003). Oral topiramate for treatment of alcohol dependence: a randomised controlled trial. Lancet, 361(9370):1677-85.

Cagetti E, Baicy KJ, Olsen RW (2004). Topiramate attenuates withdrawal signs after chronic intermittent ethanol in rats. Neuroreport, 15(1):207-10.

Baldaçara L, Cogo-Moreira H, Parreira BL et al (2016). Efficacy of topiramate in the treatment of crack cocaine dependence: a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry, 77(3):398-406.

Anthenelli RM, Heffner JL, Wong E et al (2017). A Randomized Trial Evaluating Whether Topiramate Aids Smoking Cessation and Prevents Alcohol Relapse in Recovering Alcohol‐Dependent Men. Alcohol Clin Exp Res, 41(1):197-206.

Singh M, Keer D, Klimas J et al (2016). Topiramate for cocaine dependence: a systematic review and meta‐analysis of randomized controlled trials. Addiction, 111(8):1337-46.

Umbricht A, DeFulio A, Winstanley EL et al (2014). Topiramate for cocaine dependence during methadone maintenance treatment: a randomized controlled trial. Drug Alcohol Depend, 140:92-100.

Elkashef A, Kahn R, Yu E et al (2012). Topiramate for the treatment of methamphetamine addiction: a multi‐center placebo‐controlled trial. Addiction, 107(7):1297-306.

Reis AD, Castro LA, Faria R et al (2008). Craving decrease with topiramate in outpatient treatment for cocaine dependence: an open label trial. Rev Bras Psiquiatr, 30(2):132-5.

Rass O, Umbricht A, Bigelow GE et al (2015). Topiramate impairs cognitive function in methadone-maintained individuals with concurrent cocaine dependence. Psychol Addict Behav, 29(1):237–46.

Nolan SJ, Sudell M, Tudur Smith C et al (2016). Topiramate versus carbamazepine monotherapy for epilepsy: an individual participant data review. Cochrane Database Syst Rev, 12:CD012065.

Toki T, Iwasaki T, Ishii M (2016). Topiramate Blood Levels during Polytherapy for Epilepsy in Children. Am J Ther, [Epub ahead of print].

Pirnia B, Soleimani A, Taherinakhost HR et al (2018). A Randomized Pilot Trial of Contingency-management Intervention for Patients in during Methadone Maintenance Treatment, Cash vs. Vouchers. Iran J Public Health, 47(4):618-619.

Pirnia B, Pirnia K, Aghajanpoor M et al (2018). Relationship between function of hypothalamic-pituitary-adrenal axis and executive functions in chronic methamphetamine users: A cross-sectional study. Asian J Psychiatr, 35:113-114.

Sharifi V, Assadi SM, Mohammadi MR et al (2009). A persian translation of the structured clinical interview for diagnostic and statistical manual of mental disorders: psychometric properties. Compr Psychiatry, 50(1):86-91.

Tiffany ST, Singleton E, Haertzen CA et al (1993). The development of a cocaine craving questionnaire. Drug Alcohol Depend, 34(1):19-28.

Sussner BD, Smelson DA, Rodrigues S et al (2006). The validity and reliability of a brief measure of cocaine craving. Drug Alcohol Depend, 83(3):233-7.

Johnson BA, Ait-Daoud N, Wang X-Q et al (2013). Topiramate for the treatment of cocaine addiction: a randomized clinical trial. JAMA Psychiatry, 70(12):1338-46.

Cohen J, Dervaux A, Laqueille X (2014). [Topiramate in substance-related and addictive disorders]. Presse Med, 43(9):892-901.

Rezaei F, Ghaderi E, Mardani R et al (2016). Topiramate for the management of methamphetamine dependence: a pilot randomized, double‐blind, placebo‐controlled trial. Fundam Clin Pharmacol, 30(3):282-9.

Nuijten M, Blanken P, van den Brink W et al (2014). Treatment of crack-cocaine dependence with topiramate: a randomized controlled feasibility trial in The Netherlands. Drug Alcohol Depend, 138:177-84.

IssueVol 47 No 9 (2018) QRcode
SectionOriginal Article(s)
Topiramate Anticonvulsants and adverse effects Methadone maintenance treatment Cocaine Opioid

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PIRNIA B, SOLEIMANI AA, MALEKANMEHR P, PIRNIA K, ZAHIRODDIN A. Topiramate for the Treatment of Dually Dependent on Opiates and Cocaine: A Single-center Placebo-controlled Trial. Iran J Public Health. 2018;47(9):1344-1352.